Core A: Laboratory for Cytochrome P-450 and Acetylator Metabolic Phenotyping Using Urinary Markers. The adverse consequences of an individual's exposure to environmental carcinogens will be affected by both the dose over time and the proportion of the dose that are converted into genotoxic derivatives. Since virtually all environmentally occurring carcinogens require metabolic activation to form genotoxic derivatives, a measurement of an individual's intrinsic capacity to metabolize carcinogens should provide important susceptibility information. A number of urinary markers have now been developed to assess intrinsic cytochrome P-450 expression of the isozymes IA2 and IIIA4. These enzymes are responsible for the activation of aflatoxins, PAHs and heterocyclic amines to form DNA and protein adducts. The biomarkers used to assess these enzymes are based upon caffeine and cortisol metabolism. In addition, some of the caffeine metabolites can be used to measure acetylator phenotypes in people. This pathway may be important in risk from exposure to heterocyclic amines in the diet. Thus, very safe and non-invasive procedures are available to assess these metabolic phenotypes. The specific aim of this core laboratory is to establish an automated HPLC system for the measurement of caffeine and cortisol metabolites in human urine. Data generated from these studies can be used to correlate biomarker measurements with specific metabolic parameters. This service will be available for all of the investigators in the program project grant and, during the tenure of the grant, may provide new insights into the role of metabolic phenotypes in human carcinogenesis.